I propose to investigate the relationship between leptin and trophobiast invasion. Invasion of the uterine epithelium by embryonic trophoblast ceils during early pregnancy is crucial for the establishment and development of the placenta, which is in turn necessary for healthy fetal development. Leptin is a hormone produced by adipose tissue, and in some species, the placenta, that acts as a signal of nutritional state to the reproductive system. The proposed project will attempt to characterize one of the mechanisms by which nutrition affects placental development, and increase our understanding of the role of leptin in pre-eclampsia, a common complication of pregnancy characterized by insufficient trophoblast invasion. The difference in invasivness between trophoblast ceils from early and late pregnancy will be used to study the effects of leptin. I will use primary mouse trophoblast ceils to test the hypotheses (1) that leptin promotes trophoblast invasion in placental ceils from early, but not late pregnancy and (2) that this invasion is mediated by an increase in MMP activity, which is (3) stimulated via the MAPK signaling pathway.